M6P/IGF2R gene is mutated in human hepatocellular carcinomas with loss of heterozygosity

Nat Genet. 1995 Dec;11(4):447-9. doi: 10.1038/ng1295-447.


The mannose 6-phosphate/insulin-like growth factor-II receptor (M6P/IGF2R) functions in the intracellular trafficking of lysosomal enzymes, the activation of the potent growth inhibitor, transforming growth factor beta 2, and the degradation of IGF2 (ref. 1), a mitogen often overproduced in tumours. We have recently shown that 70% of human hepatocellular tumours have loss of heterozygosity (LOH) at the M6P/IGF2R locus which maps to chromosome 6q26-q27 (ref. 8). Using a coarse screen, we have now identified point mutations in the remaining allele of 25% of human hepatocellular carcinomas (HCCs) with LOH. These mutations give rise to truncated receptor protein and significant amino acid substitutions, and provide evidence that the M6P/IGF2R gene functions as a tumour suppressor in human liver carcinogenesis.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Alternative Splicing
  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • Carcinoma, Hepatocellular / genetics*
  • Cattle
  • DNA Mutational Analysis
  • Extracellular Space / chemistry
  • Genes, Tumor Suppressor / genetics
  • Heterozygote*
  • Humans
  • Liver Neoplasms / genetics*
  • Mice
  • Molecular Sequence Data
  • Point Mutation*
  • Rats
  • Receptor, IGF Type 2 / analysis
  • Receptor, IGF Type 2 / genetics*


  • Receptor, IGF Type 2

Associated data

  • GENBANK/S80783
  • GENBANK/S80785
  • GENBANK/S80797